tbuckley/cabot-search huggingface dataset:
Feasibility of a dietary intervention to modify gut microbial metabolism in patients with hematopoietic stem cell transplantation
Authors: Mary M. Riwes, Jonathan L. Golob, John Magenau, Mengrou Shan, Gregory Dick, Thomas Braun, Thomas M. Schmidt, Attaphol Pawarode, Sarah Anand, Monalisa Ghosh, John Maciejewski, Darren King, Sung Choi, Gregory Yanik, Marcus Geer, Ethan Hillman, Costas A. Lyssiotis, Muneesh Tewari, Pavan Reddy
Journal: Nature Medicine (2023)

Abstract Evaluation of the impact of dietary intervention on gastrointestinal microbiota and metabolites after allogeneic hematopoietic stem cell transplantation (HCT) is lacking. We conducted a feasibility study as the first of a two-phase trial. Ten adults received resistant potato starch (RPS) daily from day −7 to day 100. The primary objective was to test the feasibility of RPS and its effect on intestinal microbiome and metabolites, including the short-chain fatty acid butyrate. Feasibility met the preset goal of 60% or more, adhering to 70% or more doses; fecal butyrate levels were significantly higher when participants were on RPS than when they were not ( P &lt; 0.0001). An exploratory objective was to evaluate plasma metabolites. We observed longitudinal changes in plasma metabolites compared to baseline, which were independent of RPS ( P &lt; 0.0001). However, in recipients of RPS, the dominant plasma metabolites were more stable compared to historical controls with significant difference at engraftment ( P &lt; 0.05). These results indicate that RPS in recipients of allogeneic HCT is feasible; in this study, it was associated with significant alterations in intestinal and plasma metabolites. A phase 2 trial examining the effect of RPS on graft-versus-host disease in recipients of allogeneic HCT is underway. ClinicalTrials.gov registration: NCT02763033 .
GPR84-mediated signal transduction affects metabolic function by promoting brown adipocyte activity
Authors: Xue-Nan Sun, Yu A. An, Vivian A. Paschoal, Camila O. de Souza, May-yun Wang, Lavanya Vishvanath, Lorena M.A. Bueno, Ayanna S. Cobb, Joseph A. Nieto Carrion, Madison E. Ibe, Chao Li, Harrison A. Kidd, Shiuhwei Chen, Wenhong Li, Rana K. Gupta, Da Young Oh
Journal: Journal of Clinical Investigation (2023)

The G protein-coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in a range of metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study has shed light on the pivotal role of GPR84, revealing its robust expression and functional significance within brown adipose tissue (BAT). Mice lacking GPR84 exhibited increased lipid accumulation in BAT, rendering them more susceptible to cold exposure and displaying reduced BAT activity compared with their WT counterparts. Our in vitro experiments with primary brown adipocytes from GPR84-KO mice revealed diminished expression of thermogenic genes and reduced O2 consumption. Furthermore, the application of the GPR84 agonist 6-n-octylaminouracil (6-OAU) counteracted these effects, effectively reinstating the brown adipocyte activity. These compelling in vivo and in vitro findings converge to highlight mitochondrial dysfunction as the primary cause of BAT anomalies in GPR84-KO mice. The activation of GPR84 induced an increase in intracellular Ca2+ levels, which intricately influenced mitochondrial respiration. By modulating mitochondrial Ca2+ levels and respiration, GPR84 acts as a potent molecule involved in BAT activity. These findings suggest that GPR84 is a potential therapeutic target for invigorating BAT and ameliorating metabolic disorders.
BrainStorm: a multicenter international study to tackle CNS metastases in solid tumors
Authors: Diogo Martins-Branco, Guilherme Nader-Marta, Andrea Gombos, Philippe Barthelemy, Anthony Goncalves, Edith Borcoman, Florian Clatot, Stephane Holbrechts, Eleonora De Maio D’Esposito, Claire Cheymol, Vincent Vanhaudenarde, Francois P. Duhoux, Caroline Duhem, Lore Decoster, Hannelore Denys, Florence Lefranc, Jean-Luc Canon, Paul M. Clement, Joseph Gligorov, Marianne Paesmans, Nadège Kindt, Ahmad Awada, Nuria Kotecki
Journal: Nature Medicine (2023)
Dementia after traumatic brain injury
Authors: Neil SN Graham,, David J Sharp
Journal: BMJ (2023)

This is a difficult time for people with concerns about the long term neurological effects of head injury.Increasing evidence links traumatic brain injuries (TBIs) to neurodegenerative diseases and dementia. 1 2Many high profile diagnoses of chronic traumatic encephalopathy (CTE), a specific post-traumatic dementia, have been made at post-mortem, 3 -7 contributing to general anxiety about the long term effects of even mild injuries. 8However, there are many unanswered questions which make it difficult to advise individuals of their own risk of problems and how best to promote brain health.
Nanotechnologies meeting natural sources: Engineered lipoproteins for precise brain disease theranostics
Authors: Ruoning Wang, Xinru Zhang, Kuanhan Feng, Wei Zeng, Jie Wu, Danni Sun, Ziyi Lu, Hao Feng, Liuqing Di
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Biological nanotechnologies have provided considerable opportunities in the management of malignancies with delicate design and negligible toxicity, from preventive and diagnostic to therapeutic fields. Lipoproteins, because of their inherent blood-brain barrier permeability and lesion-homing capability, have been identified as promising strategies for high-performance theranostics of brain diseases. However, the application of natural lipoproteins remains limited owing to insufficient accumulation and complex purification processes, which can be critical for individual therapeutics and clinical translation. To address these issues, lipoprotein-inspired nano drug-delivery systems (nano-DDSs), which have been learned from nature, have been fabricated to achieve synergistic drug delivery involving site-specific accumulation and tractable preparation with versatile physicochemical functions. In this review, the barriers in brain disease treatment, advantages of state-of-the-art lipoprotein-inspired nano-DDSs, and bio-interactions of such nano-DDSs are highlighted. Furthermore, the characteristics and advanced applications of natural lipoproteins and tailor-made lipoprotein-inspired nano-DDSs are summarized. Specifically, the key designs and current applications of lipoprotein-inspired nano-DDSs in the field of brain disease therapy are intensively discussed. Finally, the current challenges and future perspectives in the field of lipoprotein-inspired nano-DDSs combined with other vehicles, such as exosomes, cell membranes, and bacteria, are discussed.
Hydrogen sulfide responsive nanoplatforms: Novel gas responsive drug delivery carriers for biomedical applications
Authors: Jiafeng Zou, Zeting Yuan, Xiaojie Chen, You Chen, Min Yao, Yang Chen, Xiang Li, Yi Chen, Wenxing Ding, Chuanhe Xia, Yuzheng Zhao, Feng Gao
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Hydrogen sulfide (H2S) is a toxic, essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter. These studies have mainly focused on the production and pharmacological side effects caused by H2S. Therefore, effective strategies to remove H2S has become a key research topic. Furthermore, the development of novel nanoplatforms has provided new tools for the targeted removal of H2S. This paper was performed to review the association between H2S and disease, related H2S inhibitory drugs, as well as H2S responsive nanoplatforms (HRNs). This review first analyzed the role of H2S in multiple tissues and conditions. Second, common drugs used to eliminate H2S, as well as their potential for combination with anticancer agents, were summarized. Not only the existing studies on HRNs, but also the inhibition H2S combined with different therapeutic methods were both sorted out in this review. Furthermore, this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail. Finally, potential challenges of HRNs were proposed. This study demonstrates the excellent potential of HRNs for biomedical applications.
Longitudinal nucleocapsid antibody testing reveals undocumented SARS-CoV-2 infections in patients with lung cancer
Authors: Ananda M. Rodilla, Rajesh M. Valanparambil, Philip C. Mack, Chih-Yuan Hsu, Jazz Cagan, Sooyun C. Tavolacci, Juan Manuel Carreño, Rachel Brody, Amy Moore, Jennifer C. King, Jorge E. Gomez, Nicholas Rohs, Christian Rolfo, Paul A. Bunn, David E. Gerber, John D. Minna, Florian Krammer, Suresh S. Ramalingam, Adolfo García-Sastre, Yu Shyr, Rafi Ahmed, Fred R. Hirsch
Journal: Cancer Cell (2023)
Radial astrocyte synchronization modulates the visual system during behavioral-state transitions
Authors: Alejandro Uribe-Arias, Rotem Rozenblat, Ehud Vinepinsky, Emiliano Marachlian, Anirudh Kulkarni, David Zada, Martin Privat, Diego Topsakalian, Sarah Charpy, Virginie Candat, Sarah Nourin, Lior Appelbaum, Germán Sumbre
Journal: Neuron (2023)

Glial cells support the function of neurons. Recent evidence shows that astrocytes are also involved in brain computations. To explore whether and how their excitable nature affects brain computations and motor behaviors, we used two-photon Ca
A frontopolar-temporal circuit determines the impact of social information in macaque decision making
Authors: Ali Mahmoodi, Caroline Harbison, Alessandro Bongioanni, Andrew Emberton, Lea Roumazeilles, Jerome Sallet, Nima Khalighinejad, Matthew F.S. Rushworth
Journal: Neuron (2023)

When choosing, primates are guided not only by personal experience of objects but also by social information such as others' attitudes toward the objects. Crucially, both sources of information—personal and socially derived—vary in reliability. To choose optimally, one must sometimes override choice guidance by personal experience and follow social cues instead, and sometimes one must do the opposite. The dorsomedial frontopolar cortex (dmFPC) tracks reliability of social information and determines whether it will be attended to guide behavior. To do this, dmFPC activity enters specific patterns of interaction with a region in the mid-superior temporal sulcus (mSTS). Reversible disruption of dmFPC activity with transcranial ultrasound stimulation (TUS) led macaques to fail to be guided by social information when it was reliable but to be more likely to use it when it was unreliable. By contrast, mSTS disruption uniformly downregulated the impact of social information on behavior.
Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring
Authors: Lauren E. Colbert, Molly B. El Alam, Rui Wang, Tatiana Karpinets, David Lo, Erica J. Lynn, Timothy A. Harris, Jacob H. Elnaggar, Kyoko Yoshida-Court, Katarina Tomasic, Julianna K. Bronk, Julie Sammouri, Ananta V. Yanamandra, Adilene V. Olvera, Lily G. Carlin, Travis Sims, Andrea Y. Delgado Medrano, Tatiana Cisneros Napravnik, Madison O’Hara, Daniel Lin, Chike O. Abana, Hannah X. Li, Patricia J. Eifel, Anuja Jhingran, Melissa Joyner, Lilie Lin, Lois M. Ramondetta, Andrew M. Futreal, Kathleen M. Schmeler, Geena Mathew, Stephanie Dorta-Estremera, Jianhua Zhang, Xiaogang Wu, Nadim J. Ajami, Matthew Wong, Cullen Taniguchi, Joseph F. Petrosino, K. Jagannadha Sastry, Pablo C. Okhuysen, Sara A. Martinez, Lin Tan, Iqbal Mahmud, Philip L. Lorenzi, Jennifer A. Wargo, Ann H. Klopp
Journal: Cancer Cell (2023)

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.
The association of eicosanoids and eicosanoid-related metabolites with pulmonary hypertension
Authors: Jenna N. McNeill, Athar Roshandelpoor, Mona Alotaibi, Arrush Choudhary, Mohit Jain, Susan Cheng, Shahrooz Zarbafian, Emily S. Lau, Gregory D. Lewis, Jennifer E. Ho
Journal: European Respiratory Journal (2023)

Background Eicosanoids are bioactive lipids that regulate systemic inflammation and exert vasoactive effects. Specific eicosanoid metabolites have previously been associated with pulmonary hypertension (PH), yet their role remains incompletely understood. Methods We studied 482 participants with chronic dyspnoea who underwent clinically indicated cardiopulmonary exercise testing (CPET) with invasive haemodynamic monitoring. We performed comprehensive profiling of 888 eicosanoids and eicosanoid-related metabolites using directed non-targeted mass spectrometry, and examined associations with PH (mean pulmonary arterial pressure (mPAP) &gt;20 mmHg), PH subtypes and physiological correlates, including transpulmonary metabolite gradients. Results Among 482 participants (mean± sd age 56±16 years, 62% women), 200 had rest PH. We found 48 eicosanoids and eicosanoid-related metabolites that were associated with PH. Specifically, prostaglandin (11β-dhk-PGF2α), linoleic acid (12,13-EpOME) and arachidonic acid derivatives (11,12-DiHETrE) were associated with higher odds of PH (false discovery rate q&lt;0.05 for all). By contrast, epoxide (8(9)-EpETE), α-linolenic acid (13( S )-HOTrE(γ)) and lipokine derivatives (12,13-DiHOME) were associated with lower odds. Among PH-related eicosanoids, 14 showed differential transpulmonary metabolite gradients, with directionality suggesting that metabolites associated with lower odds of PH also displayed pulmonary artery uptake. In individuals with exercise PH, eicosanoid profiles were intermediate between no PH and rest PH, with six metabolites that differed between rest and exercise PH. Conclusions Our findings highlight the role of specific eicosanoids, including linoleic acid and epoxide derivatives, as potential regulators of inflammation in PH. Of note, physiological correlates, including transpulmonary metabolite gradients, may prioritise future studies focused on eicosanoid-related pathways as important contributors to PH pathogenesis.
Gastrointestinal pirfenidone adverse events in idiopathic pulmonary fibrosis depending on diet: the MADIET clinical trial
Authors: Maria Molina-Molina, Jessica Germaine Shull, Vanesa Vicens-Zygmunt, Pilar Rivera-Ortega, Katerina Antoniou, Francesco Bonella, Elisabetta Renzoni, Anne-Marie Russell, Toby M. Maher, Ada Vancheri, Anna Bachs, Victoria Avilés, Josep Palma, Guadalupe Bermudo, Guillermo Suarez-Cuartin, Cristian Tebé, Raul Rigo-Bonnin, Ana Montes-Worboys, Marlies Wijsenbeek, Carlo Vancheri
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>Individuals with IPF who follow a MUFA diet report a lower incidence of pirfenidone gastrointestinal adverse events than those that follow a SFA diet, which could explain the different prevalence in GI pirfenidone AEs reported by countries in IPF cohorts</b>https://bit.ly/3LuzAUJ
“From pre-COPD to COPD: a Simple, Low cost and easy to IMplement (SLIM) risk calculator.” M.J. Divo, C. Liu, F. Polverino,<i>et al</i>.<i>Eur Respir J</i>2023; 62: 2300806.
Journal: European Respiratory Journal (2023)

In the conclusion paragraph of this article, the following sentence contained an error in which "FEV 1 80-100% predicted" was stated instead of "chronic bronchitis": "In conclusion, in two different cohorts of at-risk smokers, we found that FEV 1 /FVC 0.70-0.75,smoking history ⩾30 pack-years, BMI ⩽25 kg•m -2 and FEV 1 80-100% predicted provide a reasonable estimate for the risk of developing chronic airway obstruction."The correct version of the sentence should read as follows:"In conclusion, in two different cohorts of at-risk smokers, we found that FEV 1 /FVC 0.70-0.75,smoking history ⩾30 pack-years, BMI ⩽25 kg•m -2 and chronic bronchitis provide a reasonable estimate for the risk of developing chronic airway obstruction.
Dexamethasone for preterm infants at risk of bronchopulmonary dysplasia: is timing everything?
Authors: Jasper V. Been, Sinno H.P. Simons, Jeremy A. Labrecque
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>What is the optimal timing to administer dexamethasone to preterm infants at risk of bronchopulmonary dysplasia or death? This editorial explores the opportunities and challenges of addressing this question using routine observational data.</b> https://bit.ly/3rocWqn
Charting the path to expanded access for CFTR modulator drugs: the nose knows
Authors: Christine Bear, Felix Ratjen
Journal: European Respiratory Journal (2023)

<h3>Tweetable abstract</h3> <b>The positive results reported by E. Dreano and co-workers have the potential to set a path towards improving access to highly effective CF therapies by studying <i>in vitro</i> outcomes in patient-specific nasal epithelial cell cultures</b>https://bit.ly/3Ef0rQG
The immunological landscape in pancreatic ductal adenocarcinoma and overcoming resistance to immunotherapy
Authors: Marc Hilmi, Matthieu Delaye, Milena Muzzolini, Rémy Nicolle, Jérôme Cros, Pascal Hammel, Victoire Cardot-Ruffino, Cindy Neuzillet
Journal: The Lancet. Gastroenterology & hepatology (2023)
Gestational weight change in a diverse pregnancy cohort and mortality over 50 years: a prospective observational cohort study
Authors: Stefanie N Hinkle, Sunni L Mumford, Katherine L Grantz, Pauline Mendola, James L Mills, Edwina H Yeung, Anna Z Pollack, Sonia M Grandi, Rajeshwari Sundaram, Yan Qiao, Enrique F Schisterman, Cuilin Zhang
Journal: The Lancet (2023)
Divergent tumor and immune cell reprogramming underlying immunotherapy response and immune-related adverse events in lung squamous cell carcinoma
Authors: Minjiang Chen, Pengfei Ma, Yongchang Zhang, Dong Wang, Zhuang Yu, Yujie Fu, Xiaojing Zhao, Mengzhao Wang, Guanglei Zhuang, Ying Jing
Journal: Journal for ImmunoTherapy of Cancer (2023)

Lung squamous cell carcinoma (LUSC) remains a leading cause of cancer-related deaths with few therapeutic strategies. Immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy in patients with LUSC. However, ICIs could also lead to a unique spectrum of immune-related adverse events (irAEs), which dampen the clinical outcome. In-depth characterization of the immune hallmarks of antitumor responses and irAEs remains an unmet need to maximize ICI-treatment benefits of patients. We performed single-cell RNA sequencing (scRNA-seq) on pre-ICI and on-ICI treatment tumor biopsies. We used bulk RNA-seq data of matched pretreatment/on-treatment tumors and irAE affected organs to validate observations from scRNA-seq analysis. Two independent patient cohorts were collected to determine circulating tumor necrosis factor (TNF) protein expression levels. We found that increased proportions of a macrophage subcluster with highly expressed secreted phosphoprotein 1 (SPP1) and two tumor cell subclusters in irAE patients, whereas proportions of two cytotoxic CD8+ T cell subclusters were higher in patients with partial response (PR). TNF signaling pathway was conversely associated with treatment efficacy and irAE development in most macrophage and tumor cell subclusters. Cell-cell communications for TNF ligand-receptor pairs between macrophage/T cells and tumor cells were also bidirectionally remodeled in responders versus non-responders and irAE versus non-irAE patients. Bulk RNA-seq analysis on matched pretreatment/on-treatment tumors and irAE affected organs revealed remarkably enhanced macrophage abundance and TNF signaling pathway in on-treatment tumors and organs developed irAEs. Furthermore, we observed significantly increased circulating TNF protein in plasma or serum of irAE patients but not ICI responders, based on analysis of two independent LUSC patient cohorts and one published ICI patient cohort. Our data depicts specific reprogramming of macrophage, T cells and tumor cells associated with ICI response and irAEs, elucidates divergent roles of TNF signaling in antitumor immunity and irAEs, and highlights the significance of TNF expression in irAE development in the LUSC setting.
Reply to Thomas Seisen, Morgan Rouprêt, Quoc-Dien Trinh, and Joaquim Bellmunt’s Letter to the Editor re: Martin Swinton, Neethu Billy Graham Mariam, Jean Ling Tan, et al. Bladder-Sparing Treatment with Radical Dose Radiotherapy Is an Effective Alternative to Radical Cystectomy in Patients with Clinically Node-positive Nonmetastatic Bladder Cancer. J Clin Oncol 2023;41:4406–15
Authors: Martin Swinton, Peter Hoskin, Ananya Choudhury
Journal: European Urology (2023)
Re: Martin Swinton, Neethu Billy Graham Mariam, Jean Ling Tan, et al. Bladder-Sparing Treatment with Radical Dose Radiotherapy Is an Effective Alternative to Radical Cystectomy in Patients with Clinically Node-positive Nonmetastatic Bladder Cancer. J Clin Oncol. 2023;41:4406–4415
Authors: Thomas Seisen, Morgan Rouprêt, Quoc-Dien Trinh, Joaquim Bellmunt
Journal: European Urology (2023)
Effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Madarounfa, Niger: a retrospective metagenomic analysis of a placebo-controlled trial
Authors: Drew J Schwartz, Amy Langdon, Xiaoqing Sun, Céline Langendorf, Fatou Berthé, Rebecca F Grais, Indi Trehan, Sheila Isanaka, Gautam Dantas
Journal: The Lancet Microbe (2023)

Children with severe acute malnutrition are treated with antibiotics as outpatients. We aimed to determine the effect of 7 days of amoxicillin on acute and long-term changes to the gut microbiome and antibiotic resistome in children treated for severe acute malnutrition.
Effect of the Children and Young People's Health Partnership model of paediatric integrated care on health service use and child health outcomes: a pragmatic two-arm cluster randomised controlled trial
Authors: Ingrid Wolfe, Julia Forman, Elizabeth Cecil, James Newham, Nan Hu, Rosie Satherley, Marina Soley-Bori, Julia Fox-Rushby, Simon Cousens, Raghu Lingam
Journal: The Lancet Child & Adolescent Health (2023)

Paediatric health systems across high-income countries are facing avoidable adverse outcomes and increasing demands and costs. The aim of this study was to compare the effect of an enhanced usual care model with that of an integrated health-care model that offers local health clinics for general paediatric problems and early intervention and care for children and young people with tracer conditions.